Search results for: multi-drug therapies

Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

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The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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Authors: Selamawit Hirpa, Girmay Medhin, Belaineh Girma, Muluken Melese, Alemayehu Mekonen, Pedro Suarez, Gobena Ameni

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Worldwide, there were 650,000 multi-drug resistant tuberculosis (MDR-TB) cases in 2010. Ethiopia is 15th among the 27 MDR-TB high-burden countries. A case control study was conducted at St. Peter Hospital and five health centers in Addis Ababa. Cases were MDR-TB patients who were in treatment at St. Peter Hospital during the study period. Controls were patients who were on first-line anti-TB treatment and were registered as cured or having completed treatment in the period 9 April 2009– 28 February 2010, in five health centers. A structured interview questionnaire was used to assess factors that could potentially be associated with the occurrence of MDR-TB. Factors that were significantly associated with MDR-TB: drug side effects during first-line treatment (adjusted odds ratio (AOR): 4.5, 95% CI; 1.9 - 10.5); treatment not directly observed by a health worker (AOR = 11.7, 95% CI; 4–34.3); and retreatment with the Category II regimen (P = 0.000).

Keywords: adherence to TB treatment, MDR-TB, TB treatment, TB treatment regimens

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Authors: M. Bassas, J. Grané-Morcillo, J. Segura, J.M. Soldevila

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Mental health prevention is key in a society where, according to the World Health Organization, the fourth leading cause of death worldwide is suicide. Compassion is closely linked to personal growth. It shows once again that therapies based on prevention remain an urgent and social need. In this sense, a growing body of research demonstrates how cultivating a compassionate mind can help alleviate and prevent a variety of psychological problems. In the early 21st century, there has been a boom in third-generation compassion-based therapies, although there is a lack of empirical evidence of their efficacy. This study proposes a psychotherapy method (‘Being Method’), whose central axis revolves around emotional management through the cultivation of compassion. Therefore, the objective of this research was to analyze the effectiveness of this method with regard to the emotional changes experienced when we focus on what we are concerned about through the filter of compassion. The Being Method was born from the influence of Buddhist philosophy and contemporary psychology based mainly on Western rationalist currents. A quantitative cross-sectional study has been carried out in a sample of women between 18 and 53 years old (n=47; Mage=36.02; SDage= 11.86) interested in personal growth in which the following 6 measuring instruments were administered: Peace of mind Scale (PoM), Rosenberg Self-Esteem Scale (RSES), Subjective Happiness Scale (SHS), 2 Sacles of the Compassionate Action and Engagement Scales (CAES), Coping Response Inventory for Adults (CRI-A) and Cognitive-Behavioral Strategies Evaluation Scale (MOLDES). Following an experimental method approach, participants were divided into an experimental and control group. Longitudinal analysis was also carried out through a pre-post program comparison. Pre-post comparison outcomes indicated significant differences (p<.05) between before and after the therapy in the variables Peace of Mind, Self-esteem, Happiness, Self-compassion (A-B), Compassion (A-B), in several mental molds, as well as in several coping strategies. Also, between-groups tests proved significantly higher means obtained in the experimental group. Thus, these outcomes highlighted the effectiveness of the therapy, improving all the analyzed dimensions. The social, clinical and research implications are discussed.

Keywords: being method, compassion, effectiveness, emotional management, intervention program, personal growth therapy

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Authors: Muhammad Shafi'u Adamu

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This study examined the effects of two Group Cognitive Behavioural Therapies (Cognitive Restructuring and Rational Emotive Behavioural Therapy) on Psychological Distress of awaiting-trial Inmates in Correctional Centres in North-West, Nigeria. The study had four specific objectives, four research questions, and four null hypotheses. The study used a quasi-experimental design that involved pre-test and post-test. The population comprised of all 7,962 awaiting-trial inmates in correctional centres in North-west, Nigeria. 131 awaiting trial inmates from three intact Correctional Centres were randomly selected using the census technique. The respondents were sampled and randomly put into 3 groups (CR, REBT and Control). Kessler Psychological Distress Scale (K10) was adapted for data collection in the study. The instrument was validated by experts and subjected to pilot study using Cronbach's Alpha with reliability co-efficient of 0.772. Each group received treatment for 8 consecutive weeks (60 minutes/week). Data collected from the field were subjected to descriptive statistics of mean, standard deviation and mean difference to answer the research questions. Inferential statistics of ANOVA and independent sample t-test were used to test the null hypotheses at P≤ 0.05 level of significance. Results in the study revealed that there was no significant difference among the pre-treatment mean scores of experimental and control groups. Statistical evidence also showed a significant difference among the mean sores of the three groups, and thus, results of the Post Hoc multiple-comparison test indicating the posttreatment reduction of psychological distress on the awaiting-trial inmates. Documented output also showed a significant difference between the post-treatment psychologically distressed mean scores of male and female awaiting-trial inmates, but there was no difference on those exposed to REBT. The research recommends that a standardized structured CBT counselling technique treatment should be designed for correctional centres across Nigeria, and CBT counselling techniques could be used in the treatment of PD in both correctional and clinical settings.

Keywords: awaiting-trial inmates, cognitive restructuring, correctional centres, group cognitive behavioural therapies, rational emotive behavioural therapy

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Authors: Denys Sebov, Viktoriia Korotaieva, Kateryna Markina

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The clinical advantage of the multipill combination drugs administration (polypill-strategy) over single-component drugs (monopill-strategy) has been established in patients with comorbid arterial hypertension, heart failure, chronic coronary syndrome, diabetes. It was found that polypill-strategy provides better treatment adherence in 33.4% of the patients. It was proven a significant decrease in systolic and diastolic blood pressure, as well as a decrease in dispersion index due to the stability of the blood pressure profile in patients with the polypill-strategy treatment.

Keywords: polypill, artetial hypertension, cardiovascular disease, compliance

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Authors: Sahar B. Ahmed, M. Mostafa Said, Mona I. Mohamed

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Streptozotocin (STZ) caused a significant increase in blood glucose and malondialdehyde (MDA) levels in serum accompanied by a significant decrease in blood reduced glutathione (GSH) and superoxide dismutase (SOD) activities. Also, ALT, AST, albumin and urea were markedly affected by STZ injection. The oral administration of Mango leaves extract (MLE) one hour before STZ injection was significantly improved the blood glucose level, ALT, AST activities, albumin and urea that associated with the regulation of MDA, GSH and SOD levels. The antimicrobial activity of MLE showed a significant inhibitory activity against multidrug resistant gram positive and gram negative bacteria isolated from patients in Egyptian hospitals especially Salmonella typhi and typhimurium. In conclusion, results revealed the antioxidant, hypoglycemic effect and antimicrobial potentials of MLE under investigation. Further studies will be needed to investigate the prolonged period of MLE administration and its possible side effects.

Keywords: aqueous extract of mango leaves, STZ, antioxidant, hypoglycemic effect, antimicrobial potentials.

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Authors: L. Szymanski, S. Wiak, Z. Kolacinski, G. Raniszewski, L. Pietrzak, Z. Staniszewska

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There exist more than one hundred different types of cancer, and therefore no particular treatment is offered to people struggling with this disease. The character of treatment proposed to a patient will depend on a variety of factors such as type of the cancer diagnosed, advancement of the disease, its location in the body, as well as personal preferences of a patient. None of the commonly known methods of cancer-fighting is recognised as a perfect cure, however great advances in this field have been made over last few decades. Once a patient is diagnosed with cancer, he is in need of medical care and professional treatment for upcoming months, and in most cases even for years. Among the principal modes of treatment offered by medical centres, one can find radiotherapy, chemotherapy, and surgery. All of them can be applied separately or in combination, and the relative contribution of each is usually determined by medical specialist in agreement with a patient. In addition to the conventional treatment option, every day more complementary and alternative therapies are integrated into mainstream care. There is one promising cancer modality - hyperthermia therapy which is based on exposing body tissues to high temperatures. This treatment is still being investigated and is not widely available in hospitals and oncological centres. There are two kinds of hyperthermia therapies with direct and indirect heating. The first is not commonly used due to low efficiency and invasiveness, while the second is deeply investigated and a variety of methods have been developed, including ultrasounds, infrared sauna, induction heating and magnetic hyperthermia. The aim of this work was to examine possibilities of heating magnetic nanoparticles under the influence of electromagnetic field for cancer treatment. For this purpose, multiwalled carbon nanotubes used as nanocarriers for iron particles were investigated for its heating properties. The samples were subjected to an alternating electromagnetic field with frequency range between 110-619 kHz. Moreover, samples with various concentrations of carbon nanotubes were examined. The lowest frequency of 110 kHz and sample containing 10 wt% of carbon nanotubes occurred to influence the most effective heating process. Description of hyperthermia therapy aiming at enhancing currently available cancer treatment was also presented in this paper. Most widely applied conventional cancer modalities such as radiation or chemotherapy were also described. Methods for overcoming the most common obstacles in conventional cancer modalities, such as invasiveness and lack of selectivity, has been presented in magnetic hyperthermia characteristics, which explained the increasing interest of the treatment.

Keywords: hyperthermia, carbon nanotubes, cancer colon cells, ligands

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: M. Aguilar, D. L. Araujo, A. L. Avendaño, D. C. Flores, I. Lascurain, R. A. Molina, M. Romero

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This work presents an application of social robotics, specifically the use of a NAO Robot as a tool for therapists in the treatment of Autism Spectrum Disorder (ASD). According to this, therapies approved by specialist psychologists have been developed and implemented, focusing on creating a triangulation between the robot, the child, and the therapist, aiming to improve their social and language skills, as well as communication skills and joint attention. In addition, quantitative and qualitative analysis tools have been developed and applied to prove the acceptance and the impact of the robot in the treatment of ASD.

Keywords: autism spectrum disorder, NAO robot, social and language skills, therapy

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Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

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Authors: Tareg Belali, Mosleh Abomughaid, Muhanad Alhujaily

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HNF4a is one of the steroid hormone receptor family of transcription factors with roles in the development of the liver and the regulation of several critical metabolic pathways, such as glycolysis, drug metabolism, and apolipoproteins and blood coagulation. The transcriptional potency of HNF4a is well known due to its involvement in diabetes and other metabolic diseases. However, recently HNF4a has been discovered to be closely associated with several haematological disorders, mainly because of genetic mutations, drugs, and hepatic disorders. We review HNF4a structure and function and its role in haematological disorders. We discuss possible good therapies that are based on targeting HNF4a.

Keywords: hepatocyte nuclear factor 4 alpha, HNF4a nuclear receptor, steroid hormone receptor family of transcription factors, hematological disorders

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Authors: Stephanie Newman

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Niemann-Pick Type C disease is a rare, usually fatal lysosomal storage disorder. Although clinically characterized by progressive neurodegeneration, there is also evidence of altered innate immune responses such as neuroinflammation that promote disease progression. We have initiated an investigation into whether phagocytosis, an important innate immune activity and the process by which particles are ingested is defective in NPC. Using an in vitro assay, we have shown that NPC macrophages have a deficiency in the phagocytosis of different particles. We plan to investigate the mechanistic basis for impaired phagocytosis, the contribution that this deficiency makes to disease pathology, and whether therapies that have shown in vivo benefit are able to restore phagocytic activity.

Keywords: Niemann Pick Disease C, phagocytosis, innate immunity, lysosomal storage disorder

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Authors: Varsha Gupta, Priya Datta, Gursimran Mohi, Jagdish Chander

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Fluoroquinolones form the mainstay of therapy for the treatment of infections due to Salmonella enterica subsp. enterica. There is a complex interplay between several resistance mechanisms for quinolones and various fluoroquinolones discs, giving varying results, making detection and interpretation of fluoroquinolone resistance difficult. For detection of fluoroquinolone resistance in Salmonella ssp., we compared the use of pefloxacin and nalidixic acid discs as surrogate marker. Using MIC for ciprofloxacin as the gold standard, 43.5% of strains showed MIC as ≥1 μg/ml and were thus resistant to fluoroquinoloes. Based on the performance of nalidixic acid and pefloxacin discs as surrogate marker for ciprofloxacin resistance, both the discs could correctly detect all the resistant phenotypes; however, use of nalidixic acid disc showed false resistance in the majority of the sensitive phenotypes. We have also tested newer antimicrobial agents like cefixime, imipenem, tigecycline and azithromycin against Salmonella spp. Moreover, there was a comeback of susceptibility to older antimicrobials like ampicillin, chloramphenicol, and cotrimoxazole. We can also use cefixime, imipenem, tigecycline and azithromycin in the treatment of multidrug resistant S. typhi due to their high susceptibility.

Keywords: salmonella, pefloxacin, surrogate marker, chloramphenicol

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Authors: Temesgen Geremew

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Functionalized nanoparticles have emerged as a revolutionary platform for drug delivery, offering significant advantages over traditional methods. By strategically modifying their surface properties, these nanoparticles can be designed to target specific tissues and cells, significantly reducing off-target effects and enhancing therapeutic efficacy. This targeted approach allows for lower drug doses, minimizing systemic exposure and potential side effects. Additionally, functionalization enables controlled release of the encapsulated drug, improving drug stability and reducing the frequency of administration, leading to improved patient compliance. This work explores the immense potential of functionalized nanoparticles in revolutionizing drug delivery, addressing limitations associated with conventional therapies and paving the way for personalized medicine with precise and targeted treatment strategies.

Keywords: nanoparticles, drug, nanomaterials, applications

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Authors: Kristina Karapetyan, Flora Tkhruni, Tsovinar Balabekyan, Arevik Israyelyan, Tatyana Khachatryan

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The ability of the lactic acid bacteria (LAB) to prevent and cure a variety of diseases, their protective role against infections and colonization of pathogenic microorganisms in the digestive tract, has lead to the coining of the term probiotics or pro-life. LAB inhibiting the growth of pathogenic and food spoilage microorganisms, maintaining the nutritive quality and improving the shelf life of foods. They have also been used as flavor and texture producers. Enterococcus strains have been used for treatment of diseases such as diarrhea or antibiotic associated diarrhea, inflammatory pathologies that affect colon such as irritable bowel syndrome, or immune regulation, diarrhea caused by antibiotic treatments. The obtaining and investigation of biological properties of proteinoceous antibiotics, on the basis of probiotic LAB shown, that bacteriocins, metabiotics, and peptides of LAB represent bactericides have a broad range of activity and are excellent candidates for development of new prophylactic and therapeutic substances to complement or replace conventional antibiotics. The genotyping by 16S rRNA sequencing for LAB were used. Cell free culture broth (CFC) broth was purified by the Gel filtration method on the Sephadex Superfine G 25 resin. Antimicrobial activity was determined by spot-on-lawn method and expressed in arbitrary units (AU/ml). The diversity of multidrug-resistance (MDR) of pathogenic strains to antibiotics, most widely used for treatment of human diseases in the Republics of Armenia and Nagorno Karabakh were examined. It was shown, that difference of resistance of pathogens to antibiotics depends on their isolation sources. The influences of partially purified antimicrobial preparations (AMP), obtained from the different strains of Enterococcus genus on the growth of MDR pathogenic bacteria were investigated. It was shown, that bacteriocin containing partially purified preparations, obtained from different strains of Enterococcus faecium and durans species, possess bactericidal or bacteriostatic activity against antibiotic resistant intestinal, spoilage and food-borne pathogens such as Listeria monocytogenes, Staphylococcus aureus, E. coli, and Salmonella. Endemic strains of LAB, isolated from Matsoni made from donkey, buffalo and goat milk, shown broad spectrum of activity against food spoiling microorganisms, moulds and fungi, such as Salmonella sp., Esherichia coli, Aspergillus and Penicillium species. Highest activity against MDR pathogens shown bacteria, isolated from goat milk products. High stability of the investigated strains of the genus Enerococcus, isolated from samples of matsun from different regions of Nagorno-Karabakh (NKR) to the antibiotics was shown. The obtained data show high stability of the investigated different strains of the genus Enerococcus. The high genetic diversity in Enterococcus group suggests adaptations for specific mutations in different environments. Thus, endemic strains of LAB are able to produce bacteriocins with high and different inhibitory activity against broad spectrum of microorganisms isolated from different sources and belong to different taxonomic group. Prospect of the use of certain antimicrobial preparations against pathogenic strains is obvious. These AMP can be applied for long term use against different etiology antibiotic resistant pathogens for prevention or treatment of infectional diseases as an alternative to antibiotics.

Keywords: antimicrobial biopreparation, endemic lactic acid bacteria, intra-species diversity, multidrug resistance of pathogens

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Authors: Saheb Yousefi, Kim T. Zebehazy, Parviz Sharifi Daramadi, Tahereh Najafi Fard, Kevin Murfitt

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Context: Children with visual impairments often face challenges in their cognitive, motor, and social development. Sensory-motor and spatial perception therapies can be beneficial for these children, but many existing programs only focus on a limited set of therapies. This study aims to investigate the effectiveness of a rehabilitation program for sensory- motor and spatial perception in reducing the fear of mobility in visually impaired children. Research Aim: The aim of this study is to determine if a rehabilitation program based on parent-child interaction can reduce the fear of mobility in visually impaired children. Methodology: This study uses a semi-experimental approach with an uneven control group design. Visually impaired children aged 10 to 14 and their parents from the Board of the Blind and Visually Impaired in Tehran Province were included in the study. The sample was divided into experimental and control groups, with a total of 30 participants. The experimental group participated in a rehabilitation program for sensory-motor and spatial perception based on parent-child interaction, while the control group did not receive this intervention. Data was collected using questionnaires on transportation issues and analyzed using multivariate and univariate mixed analysis of variance tests. Findings: The analysis of the data showed that the fear of movement was significantly improved in the experimental group compared to the control group after the intervention. Theoretical Importance: This study highlights the effectiveness of a rehabilitation program for sensory- motor and spatial perception based on parent-child interaction in reducing the fear of mobility in visually impaired children. It contributes to the existing knowledge by demonstrating the positive impact of this type of intervention on the cognitive, motor, and social development of these children. Data Collection and Analysis Procedures: Data was collected through the use of questionnaires administered to the children before and after the intervention. The data was analyzed using multivariate and univariate mixed analysis of variance tests to examine the effects of the rehabilitation program. Questions Addressed: This study addresses the question of whether a rehabilitation program based on parent-child interaction can reduce the fear of mobility in visually impaired children. Conclusion: The findings of this study support the effectiveness of the sensory-motor and spatial perception rehabilitation program based on parent-child interaction in reducing the fear of movement in visually impaired children. This intervention can be considered as a suitable method to enhance the fear of mobility in these children.

Keywords: vision impairment, sensory-motor rehabilitation, space perception, parent-child interaction, fear of movement.

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Authors: Lilia Edit Aparicio Pico, Paulo Cesar Coronado Sánchez, Roberto Ferro Escobar

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This paper presents the implementation of telemedicine services for physiotherapy, occupational therapy, and speech therapy rehabilitation, utilizing telebroadcasting of audiovisual content to enhance comprehensive patient recovery in rural areas of San Vicente del Caguán municipality, characterized by high levels of social conflict in Colombia. The region faces challenges such as dysfunctional problems, physical rehabilitation needs, and a high prevalence of hearing diseases, leading to neglect and substandard health services. Limited access to healthcare due to communication barriers and transportation difficulties exacerbates these issues. To address these challenges, a research initiative was undertaken to leverage information and communication technologies (ICTs) to improve healthcare quality and accessibility for this vulnerable population. The primary objective was to develop a tele-rehabilitation system to provide asynchronous online therapies and teleconsultation services for patient follow-up during the recovery process. The project comprises two components: Communication systems and human development. A technological component involving the establishment of a wireless network connecting rural centers and the development of a mobile application for video-based therapy delivery. Communications systems will be provided by a radio link that utilizes internet provided by the Colombian government, located in the municipality of San Vicente del Caguán to connect two rural centers (Pozos and Tres Esquinas) and a mobile application for managing videos for asynchronous broadcasting in sidewalks and patients' homes. This component constitutes an operational model integrating information and telecommunications technologies. The second component involves pedagogical and human development. The primary focus is on the patient, where performance indicators and the efficiency of therapy support were evaluated for the assessment and monitoring of telerehabilitation results in physical, occupational, and speech therapy. They wanted to implement a wireless network to ensure audiovisual content transmission for tele-rehabilitation, design audiovisual content for tele-rehabilitation based on services provided by the ESE Hospital San Rafael in physiotherapy, occupational therapy, and speech therapy, develop a software application for fixed and mobile devices enabling access to tele-rehabilitation audiovisual content for healthcare personnel and patients and finally to evaluate the technological solution's contribution to the ESE Hospital San Rafael community. The research comprised four phases: wireless network implementation, audiovisual content design, software application development, and evaluation of the technological solution's impact. Key findings include the successful implementation of virtual teletherapy, both synchronously and asynchronously, and the assessment of technological performance indicators, patient evolution, timeliness, acceptance, and service quality of tele-rehabilitation therapies. The study demonstrated improved service coverage, increased care supply, enhanced access to timely therapies for patients, and positive acceptance of teletherapy modalities. Additionally, the project generated new knowledge for potential replication in other regions and proposed strategies for short- and medium-term improvement of service quality and care indicators

Keywords: e-health, medical informatics, telemedicine, telerehabilitation, virtual therapy

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Authors: Marina Nosik, Irina Rymanova, Konstantin Ryzhov, Joan Yarovaya, Alexander Sobkin

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Tuberculosis (TB) associated with HIV is one of the top causes of death worldwide. However, early detection and treatment of TB in HIV-infected individuals significantly reduces the risk of developing severe forms of TB and mortality. The goal of the study was to analyze the peculiarities of TB associated with HIV infection. Over the period of 2015-2016 a retrospective cohort study was conducted among 377 patients with TB/HIV co-infection who attended the Moscow Tuberculosis Clinic. The majority of the patients was male (64,5%). The median age was: men 37,9 (24÷62) and women 35,4 (22÷72) years. The most prevalent age group was 30-39 years both for men and women (73,3% and 54,7%, respectively). The ratio of patients in age group 50-59 and senior was 3,9%. Socioeconomic status of patients was rather low: only 2.3% of patients had a university degree; 76,1% was unemployed (of whom 21,7% were disabled). Most patients had disseminated pulmonary tuberculosis in the phase of infiltration/ decay (41,5%). The infiltrative TB was detected in 18,9% of patients; 20,1% patients had tuberculosis of intrathoracic lymph nodes. The occurrence of MDR-TB was 16,8% and XDR-TB – 17,9%. The number of HIV-positive patients with newly diagnosed TB was n=261(69,2%). The active TB-form (MbT+) among new TB/HIV cases was 44,7 %. The severe clinical forms of TB and a high TB incidence rate among HIV-infected individuals alongside with a large number of cases of newly diagnosed tuberculosis, indicate the need for more intense interaction with TB services for timely diagnosis of TB which will optimize treatment outcomes.

Keywords: HIV, tuberculosis (TB), TB associated with HIV, multidrug-resistant TB (MDR-TB)

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Authors: Soheir Mohamed Fathey

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Biofilms are complex biological communities which are hard to be eliminated by conventional antibiotic administration and implemented in eighty percent of humans infections. Green remedies have been used for centuries and have shown obvious effects in hindering and combating microbial biofilm infections. Nowadays, there has been a growth in the number of researches on the anti-biofilm performance of natural agents such as plant essential oil (EOs) and propolis. In this study, we investigated the antibiofilm performance of various natural agents, including four essential oils (EOs), cinnamon (Cinnamomum cassia), tea tree (Melaleuca alternifolia), and clove (Syzygium aromaticum), as well as propolis versus the biofilm of both Gram-positive pathogenic bacterium Staphylococcus aureus and Gram-negative pathogenic bacterium Pseudomonas aeruginosa which are major human and animal pathogens rendering a high risk due to their biofilm development ability. The antibiofilm activity of the tested agents was evaluated by crystal violet staining assay and detected by scanning electron and fluorescent microscopy. Antibiofilm performance declared a potent effect of the tested products versus the tested bacterial biofilms.

Keywords: biofilm, essential oils, electron microscopy, fluorescent

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Authors: Farman Ali, Asif Mahmood

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The utilization of genetic markers in prostate cancer management represents a significant advance in personalized medicine, offering the potential for more precise diagnosis and tailored treatment strategies. This paper explores the pivotal role of genetic markers in the diagnosis and treatment of prostate cancer, emphasizing their contribution to the identification of individual risk profiles, tumor aggressiveness, and response to therapy. By integrating current research findings, we discuss the application of genetic markers in developing targeted therapies and the implications for patient outcomes. Despite the promising advancements, challenges such as accessibility, cost, and the need for further validation in diverse populations remain. The paper concludes with an outlook on future directions, underscoring the importance of genetic markers in revolutionizing prostate cancer care.

Keywords: prostate cancer, genetic markers, personalized medicine, BRCA1 and BRCA2

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Authors: Kiran Fatima, Kashif Ali

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Staphylococcus aureus is an opportunistic human as well as animal pathogen that causes a variety of diseases. A total of 70 staphylococci isolates were obtained from soil, water, yogurt, and clinical samples. The likely staphylococci clinical isolates were identified phenotypically by different biochemical tests. Molecular identification was done by PCR using species-specific 16S rRNA primer pairs, and finally, 50 isolates were found to be positive as Staphylococcus aureus, sciuri, xylous and cohnii. Screened isolates were further analyzed by several microbiological diagnostics tests, including gram staining, coagulase, capsule, hemolysis, fermentation of glucose, lactose, maltose, and sucrose tests enzymatic reactions. It was found that 78%, 81%, and 51% of isolates were positive for gelatin hydrolysis, protease, and lipase activities, respectively. Antibiogram analysis of isolated Staphylococcus aureus strains with respect to different antimicrobial agents revealed resistance patterns ranging from 57 to 96%. Our study also shows 70% of strains to be MRSA, 54.3% as VRSA, and 54.3% as both MRSA and VRSA. All the identified isolates were subjected to detection of mecA, nuc, and hlb genes, and 70%, 84%, and 40% were found to harbour mecA, nuc, and hlb genes, respectively. The current investigation is highly important and informative for the high-level multidrug-resistant Staphylococcus aureus infections inclusive also of methicillin and vancomycin.

Keywords: MRSA, VRSA, mecA, MSSA

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Authors: Sahira Nsayef Muslim, Israa M. S. Al-Kadmy, Nadheema Hammood Hussein, Alaa Naseer Mohammed Ali, Buthainah Mohammed Taha, Rayim Sabah Abbood, Sarah Naji Aziz

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A novel strain of Bacillus licheniformis isolated from spoilt cucumber and pepper samples have the ability to produce the chitosanase enzyme when grown on chitosan substrate. Chitosanase was purified to homogeneity with a recovery yield of 35.71% and 5.5 fold of purification by using ammonium sulfate at 45% saturation followed by ion exchange chromatography on DEAE-cellulose column and gel filtration chromatography on Sephadex G-100 column. The purified chitosanase inhibited the biofilm formation ability for all Gram-negative and Gram-positive biofilm-forming bacteria (biofilm producers) after using Congo Red agar and Microtiter plates methods. Highly antibiofilm of chitosanase recorded against Pseudomonas aeruginosa followed by Klebsiella pneumoniae with reduction of biofilm formation ratio to 22 and 29%, respectively compared with (100)% of control. Thus, chitosanase has promising benefit as antibiofilm agent against biofilm forming pathogenic bacteria and has promising application as alternative antibiofilm agents to combat the growing number of multidrug-resistant pathogen-associated infections, especially in situation where biofilms are involved.

Keywords: chitosanase, Bacillus licheniformis, vegetables, biofilm

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Authors: Gagan Dhawan

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Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

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Authors: Chester Joshua V. Saldana, Yolanda A. Ilagan

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This study determines the prevalence of Salmonella from retail dressed chickens using chicken wings as samples in five wet city markets of Cavite, Philippines, compares the prevalence among the markets' samples and determines the serotypes and antibiotic resistance pattern of Salmonella isolates. The overall prevalence of Salmonella in five wet markets in Cavite was 13.33 percent. Samples from Bacoor yielded the highest prevalence rate of 26.6 percent, followed by Imus (23.3%), Dasmarinas (11.6%), Trece Martires (3.3%) and Tagaytay (1.6%). Seven serotypes (serogroups B, C2, C3, D1 and E1) were isolated which include Salmonella weltevreden, S. derby, S. newport, S. albany, S. typhimurium, and S. enteritidis. Salmonella weltevreden was the predominant serotype while S. typhi and S. albany were the least common. Among the 15 antibiotics tested, resistance to ampicillin, tetracycline, and cephalexin was exhibited by all the isolates while 5 percent showed resistance to gentamicin, 2.5 percent to streptomycin and 12.5 percent to nitrofurantoin. One isolate was resistant to four antibiotics whereas most isolates of S. enteritidis were resistant to 2 to 5 antibiotics. Four resistance patterns were recorded. This study revealed the emergence of multidrug-resistant Salmonella serotypes from chicken meat in Cavite, Philippines.

Keywords: antibiotics, dressed chickens, resistance patterns, Salmonella serovars

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Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev

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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.

Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis

Procedia PDF Downloads 257

Authors: Jasmeet Kaur, Anup Singh, Shashikant Iyengar, Arun Kumar, Ira Sahay

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Latent autoimmune diabetes in adults (LADA) is an irreversible autoimmune disease that affects insulin production. LADA is characterized by the production of Glutamic acid decarboxylase (GAD) antibodies, which is similar to type 1 diabetes. Individuals with LADA may eventually develop overt diabetes and require insulin. In this condition, the pancreas produces little or no insulin, which is a hormone used by the body to allow glucose to enter cells and produce energy. While type 1 diabetes was traditionally associated with children and teenagers, its prevalence has increased in adults as well. LADA is frequently misdiagnosed as type 2 diabetes, especially in adulthood when type 2 diabetes is more common. LADA develops in adulthood, usually after age 30. Managing LADA involves metabolic control with exogenous insulin and prolonging the life of surviving beta cells, thereby slowing the disease's progression. This case study examines the impact of approximately 3 months of low-carbohydrate dietary intervention in a 42-year-old woman with LADA who was initially misdiagnosed as having type 2 diabetes. Her c-peptide was 0.13 and her HbA1c was 9.3% when this trial began. Low-carbohydrate interventions have been shown to improve blood sugar levels, including fasting, post-meal, and random blood sugar levels, as well as haemoglobin levels, blood pressure, energy levels, sleep quality, and satiety levels. The use of low-carbohydrate dietary intervention significantly reduces both hypo- and hyperglycaemia events. During the 3 months of the study, there were 2 to 3 hyperglycaemic events owing to physical stress and a single hypoglycaemic event. Low-carbohydrate dietary therapies lessen insulin dose inaccuracy, which explains why there were fewer hyperglycaemic and hypoglycaemic events. In three months, the glycated haemoglobin (HbA1c) level was reduced from 9.3% to 6.3%. These improvements occur without the need for caloric restriction or physical activity. Stress management was crucial aspect of the treatment plan as stress-induced neuroendocrine hormones can cause immunological dysregulation. Additionally, supplements that support immune system and reduce inflammation were used as part of the treatment during the trial. Long-term studies are needed to track disease development and corroborate the claim that such dietary treatments can prolong the honeymoon phase in LADA. Various factors can contribute to additional autoimmune attacks, so measuring c-peptide is crucial on a regular basis to determine whether insulin levels need to be adjusted.

Keywords: autoimmune, diabetes, LADA, low_carb, nutrition

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Authors: Padma Chutoo, Elena Kulinskaya, Ilyas Bakbergenuly, Nicholas Steel, Dmitri Pchejetski

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Stroke is associated with a significant risk of morbidity and mortality. There is scarcity of research on the long-term survival after first-ever ischaemic stroke (IS) events in England with regards to effects of different medical therapies and comorbidities. The objective of this study was to model the all-cause mortality after an IS diagnosis in the adult population of England. Using a retrospective case-control design, we extracted the electronic medical records of patients born prior to or in year 1960 in England with a first-ever ischaemic stroke diagnosis from January 1986 to January 2017 within the Health and Improvement Network (THIN) database. Participants with a history of ischaemic stroke were matched to 3 controls by sex and age at diagnosis and general practice. The primary outcome was the all-cause mortality. The hazards of the all-cause mortality were estimated using a Weibull-Cox survival model which included both scale and shape effects and a shared random effect of general practice. The model included sex, birth cohort, socio-economic status, comorbidities and medical therapies. 20,250 patients with a history of IS (cases) and 55,519 controls were followed up to 30 years. From 2008 to 2015, the one-year all-cause mortality for the IS patients declined with an absolute change of -0.5%. Preventive treatments to cases increased considerably over time. These included prescriptions of statins and antihypertensives. However, prescriptions for antiplatelet drugs decreased in the routine general practice since 2010. The survival model revealed a survival benefit of antiplatelet treatment to stroke survivors with hazard ratio (HR) of 0.92 (0.90 – 0.94). IS diagnosis had significant interactions with gender and age at entry and hypertension diagnosis. IS diagnosis was associated with high risk of all-cause mortality with HR= 3.39 (3.05-3.72) for cases compared to controls. Hypertension was associated with poor survival with HR = 4.79 (4.49 - 5.09) for hypertensive cases relative to non-hypertensive controls, though the detrimental effect of hypertension has not reached significance for hypertensive controls, HR = 1.19(0.82-1.56). This study of English primary care data showed that between 2008 and 2015, the rates of prescriptions of stroke preventive treatments increased, and a short-term all-cause mortality after IS stroke declined. However, stroke resulted in poor long-term survival. Hypertension, a modifiable risk factor, was found to be associated with poor survival outcomes in IS patients. Antiplatelet drugs were found to be protective to survival. Better efforts are required to reduce the burden of stroke through health service development and primary prevention.

Keywords: general practice, hazard ratio, health improvement network (THIN), ischaemic stroke, multiple imputation, Weibull-Cox model.

Procedia PDF Downloads 147

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

Procedia PDF Downloads 179